{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T15:56:59Z","timestamp":1776268619576,"version":"3.50.1"},"reference-count":69,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2012,7,19]],"date-time":"2012-07-19T00:00:00Z","timestamp":1342656000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0041170","type":"journal-article","created":{"date-parts":[[2012,7,20]],"date-time":"2012-07-20T01:36:36Z","timestamp":1342748196000},"page":"e41170","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":57,"title":["Modulation of MicroRNA-194 and Cell Migration by HER2-Targeting Trastuzumab in Breast Cancer"],"prefix":"10.1371","volume":"7","author":[{"given":"Xiao-Feng","family":"Le","sequence":"first","affiliation":[]},{"given":"Maria I.","family":"Almeida","sequence":"additional","affiliation":[]},{"given":"Weiqun","family":"Mao","sequence":"additional","affiliation":[]},{"given":"Riccardo","family":"Spizzo","sequence":"additional","affiliation":[]},{"given":"Simona","family":"Rossi","sequence":"additional","affiliation":[]},{"given":"Milena S.","family":"Nicoloso","sequence":"additional","affiliation":[]},{"given":"Shu","family":"Zhang","sequence":"additional","affiliation":[]},{"given":"Yun","family":"Wu","sequence":"additional","affiliation":[]},{"given":"George A.","family":"Calin","sequence":"additional","affiliation":[]},{"given":"Robert C.","family":"Bast","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2012,7,19]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1128\/MCB.9.3.1165","article-title":"p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor.","volume":"9","author":"RM Hudziak","year":"1989","journal-title":"Mol Cell Biol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1200\/JCO.1999.17.9.2639","article-title":"Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease.","volume":"17","author":"MA Cobleigh","year":"1999","journal-title":"J Clin Oncol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1200\/JCO.20.3.719","article-title":"Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer.","volume":"20","author":"CL Vogel","year":"2002","journal-title":"J Clin Oncol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1200\/JCO.2001.19.10.2722","article-title":"Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer.","volume":"19","author":"HJ Burstein","year":"2001","journal-title":"J Clin Oncol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1200\/JCO.2001.19.10.2587","article-title":"Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification.","volume":"19","author":"AD Seidman","year":"2001","journal-title":"J Clin Oncol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1056\/NEJM200103153441101","article-title":"Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2.","volume":"344","author":"DJ Slamon","year":"2001","journal-title":"N Engl J Med"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1200\/JCO.2002.07.058","article-title":"Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer.","volume":"20","author":"FJ Esteva","year":"2002","journal-title":"J Clin Oncol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0093-7754(01)90281-7","article-title":"Integration of trastuzumab into adjuvant systemic therapy of breast cancer: ongoing and planned clinical trials.","volume":"28","author":"GN Hortobagyi","year":"2001","journal-title":"Semin Oncol"},{"key":"ref9","doi-asserted-by":"crossref","DOI":"10.3816\/CBC.2002.n.028","article-title":"Resistance to trastuzumab: a necessary evil or a temporary challenge?","author":"F Cardoso","year":"2002"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/bcr1612","article-title":"HER2 therapy: molecular mechanisms of trastuzumab resistance.","volume":"8","author":"R Nahta","year":"2006","journal-title":"Breast Cancer Res"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1093\/annonc\/12.suppl_1.S21","article-title":"Modulation of p27\/Cdk2 complex formation through 4D5-mediated inhibition of HER2 receptor signaling.","volume":"12","author":"HA Lane","year":"2001","journal-title":"Ann Oncol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.4161\/cc.5.15.3007","article-title":"Anti-HER2 antibody trastuzumab inhibits CDK2-mediated NPAT and histone H4 expression via the PI3K pathway.","volume":"5","author":"XF Le","year":"2006","journal-title":"Cell Cycle"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"23441","DOI":"10.1074\/jbc.M300848200","article-title":"The role of cyclin-dependent kinase inhibitor p27Kip1 in anti-HER2 antibody-induced G1 cell cycle arrest and tumor growth inhibition.","volume":"278","author":"XF Le","year":"2003","journal-title":"J Biol Chem"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1074\/jbc.M403080200","article-title":"Genes affecting the cell cycle, growth, maintenance, and drug sensitivity are preferentially regulated by anti-HER2 antibody through phosphatidylinositol 3-kinase-AKT signaling.","volume":"280","author":"XF Le","year":"2005","journal-title":"J Biol Chem"},{"key":"ref15","first-page":"260","article-title":"Anti-HER2 antibody and heregulin suppress growth of HER2-overexpressing human breast cancer cells through different mechanisms.","volume":"6","author":"XF Le","year":"2000","journal-title":"Clin Cancer Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"87","DOI":"10.4161\/cc.4.1.1360","article-title":"HER2-targeting antibodies modulate the cyclin-dependent kinase inhibitor p27Kip1 via multiple signaling pathways.","volume":"4","author":"XF Le","year":"2005","journal-title":"Cell Cycle"},{"key":"ref17","first-page":"3522","article-title":"Differential signaling by an anti-p185(HER2) antibody and heregulin.","volume":"60","author":"XF Le","year":"2000","journal-title":"Cancer Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.ccr.2009.03.020","article-title":"Ligand-independent HER2\/HER3\/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941.","volume":"15","author":"TT Junttila","year":"2009","journal-title":"Cancer Cell"},{"key":"ref19","first-page":"4132","article-title":"Herceptin-induced inhibition of phosphatidylinositol-3 kinase and Akt Is required for antibody-mediated effects on p27, cyclin D1, and antitumor action.","volume":"62","author":"FM Yakes","year":"2002","journal-title":"Cancer Res"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ccr.2004.06.022","article-title":"PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients.","volume":"6","author":"Y Nagata","year":"2004","journal-title":"Cancer Cell"},{"key":"ref21","first-page":"89","article-title":"Combination therapy with trastuzumab (Herceptin) and cisplatin for chemoresistant metastatic breast cancer: evidence for receptor-enhanced chemosensitivity.","volume":"26","author":"MD Pegram","year":"1999","journal-title":"Semin Oncol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"6986","DOI":"10.1038\/sj.onc.1209685","article-title":"HER2 signaling modulates the equilibrium between pro- and antiangiogenic factors via distinct pathways: implications for HER2-targeted antibody therapy.","volume":"25","author":"XF Wen","year":"2006","journal-title":"Oncogene"},{"key":"ref23","article-title":"The inhibitory effects of trastuzumab on corneal neovascularization.","author":"M Guler","year":"2009"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.4161\/cc.7.23.7212","article-title":"Specific blockade of VEGF and HER2 pathways results in greater growth inhibition of breast cancer xenografts that overexpress HER2.","volume":"7","author":"XF Le","year":"2008","journal-title":"Cell Cycle"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1002\/cncr.11656","article-title":"Combined trastuzumab and paclitaxel treatment better inhibits ErbB-2-mediated angiogenesis in breast carcinoma through a more effective inhibition of Akt than either treatment alone.","volume":"98","author":"KS Klos","year":"2003","journal-title":"Cancer"},{"key":"ref26","first-page":"1673","article-title":"The effect of trastuzumab\/docatexel combination on breast cancer angiogenesis: dichotomus effect predictable by the HIFI alpha\/VEGF pre-treatment status?","volume":"23","author":"MI Koukourakis","year":"2003","journal-title":"Anticancer Res"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/416279b","article-title":"Tumour biology: herceptin acts as an anti-angiogenic cocktail.","volume":"416","author":"Y Izumi","year":"2002","journal-title":"Nature"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"S35","DOI":"10.1093\/annonc\/12.suppl_1.S35","article-title":"Mechanism of action of anti-HER2 monoclonal antibodies.","volume":"12","author":"J Baselga","year":"2001","journal-title":"Ann Oncol"},{"key":"ref29","first-page":"4744","article-title":"Trastuzumab (herceptin), a humanized anti-Her2 receptor monoclonal antibody, inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells.","volume":"61","author":"MA Molina","year":"2001","journal-title":"Cancer Res"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/sj.bjc.6602930","article-title":"Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?","volume":"94","author":"L Arnould","year":"2006","journal-title":"Br J Cancer"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1479-5876-6-25","article-title":"Correlation between NK function and response to trastuzumab in metastatic breast cancer patients.","volume":"6","author":"A Beano","year":"2008","journal-title":"J Transl Med"},{"key":"ref32","first-page":"5813","article-title":"Impaired antibody-dependent cellular cytotoxicity mediated by herceptin in patients with gastric cancer.","volume":"62","author":"K Kono","year":"2002","journal-title":"Cancer Res"},{"key":"ref33","first-page":"5703","article-title":"Enhanced sensitization to taxol-induced apoptosis by herceptin pretreatment in ErbB2-overexpressing breast cancer cells.","volume":"62","author":"S Lee","year":"2002","journal-title":"Cancer Res"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1158\/1078-0432.CCR-05-0754","article-title":"Herceptin sensitizes ErbB2-overexpressing cells to apoptosis by reducing antiapoptotic Mcl-1 expression.","volume":"12","author":"ES Henson","year":"2006","journal-title":"Clin Cancer Res"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1200\/JCO.2005.00.661","article-title":"Neoadjuvant trastuzumab induces apoptosis in primary breast cancers.","volume":"23","author":"SK Mohsin","year":"2005","journal-title":"J Clin Oncol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/S0092-8674(01)00616-X","article-title":"microRNAs: tiny regulators with great potential.","volume":"107","author":"V Ambros","year":"2001","journal-title":"Cell"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nrg1379","article-title":"MicroRNAs: small RNAs with a big role in gene regulation.","volume":"5","author":"L He","year":"2004","journal-title":"Nat Rev Genet"},{"key":"ref38","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2009.04.040","article-title":"SnapShot: MicroRNAs in Cancer.","author":"R Spizzo","year":"2009"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/nrc2619","article-title":"MicroRNAs\u2013the micro steering wheel of tumour metastases.","volume":"9","author":"MS Nicoloso","year":"2009","journal-title":"Nat Rev Cancer"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s12307-010-0037-4","article-title":"The Roles of MicroRNAs in the Cancer Invasion-Metastasis Cascade.","volume":"3","author":"XF Le","year":"2010","journal-title":"Cancer Microenviron"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.ejca.2009.10.027","article-title":"MicroRNAs: predictors and modifiers of chemo- and radiotherapy in different tumour types.","volume":"46","author":"R Hummel","year":"2010","journal-title":"Eur J Cancer"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.molmed.2011.04.003","article-title":"MicroRNA pharmacogenomics: post-transcriptional regulation of drug response.","volume":"17","author":"JL Rukov","year":"2011","journal-title":"Trends Mol Med"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1158\/1535-7163.MCT-10-0397","article-title":"Resistance may not be futile: microRNA biomarkers for chemoresistance and potential therapeutics.","volume":"9","author":"KE Allen","year":"2010","journal-title":"Mol Cancer Ther"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"15524","DOI":"10.1073\/pnas.242606799","article-title":"Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia.","volume":"99","author":"GA Calin","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1158\/1535-7163.MCT-07-0109","article-title":"Roles of human epidermal growth factor receptor 2, c-jun NH2-terminal kinase, phosphoinositide 3-kinase, and p70 S6 kinase pathways in regulation of cyclin G2 expression in human breast cancer cells.","volume":"6","author":"XF Le","year":"2007","journal-title":"Mol Cancer Ther"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"4980","DOI":"10.1002\/cncr.25426","article-title":"Dasatinib induces autophagic cell death in human ovarian cancer.","volume":"116","author":"XF Le","year":"2010","journal-title":"Cancer"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"15805","DOI":"10.1073\/pnas.0707628104","article-title":"MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B.","volume":"104","author":"M Fabbri","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1002\/cm.970030509","article-title":"Talin: a cytoskeletal component concentrated in adhesion plaques and other sites of actin-membrane interaction.","volume":"3","author":"K Burridge","year":"1983","journal-title":"Cell Motil"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/308744a0","article-title":"An interaction between vinculin and talin.","volume":"308","author":"K Burridge","year":"1984","journal-title":"Nature"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/nature03702","article-title":"MicroRNA expression profiles classify human cancers.","volume":"435","author":"J Lu","year":"2005","journal-title":"Nature"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1101\/gr.2845604","article-title":"MicroRNA expression detected by oligonucleotide microarrays: system establishment and expression profiling in human tissues.","volume":"14","author":"O Barad","year":"2004","journal-title":"Genome Res"},{"key":"ref52","first-page":"415","article-title":"Regulatory interaction of HNF1-alpha to microRNA-194 gene during intestinal epithelial cell differentiation.","author":"K Hino","year":"2007"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1261\/rna.810208","article-title":"Inducible expression of microRNA-194 is regulated by HNF-1alpha during intestinal epithelial cell differentiation.","volume":"14","author":"K Hino","year":"2008","journal-title":"Rna"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1002\/hep.23915","article-title":"miR-194 is a marker of hepatic epithelial cells and suppresses metastasis of liver cancer cells in mice.","volume":"52","author":"Z Meng","year":"2010","journal-title":"Hepatology"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"10094","DOI":"10.1158\/0008-5472.CAN-08-1569","article-title":"p53-Responsive micrornas 192 and 215 are capable of inducing cell cycle arrest.","volume":"68","author":"CJ Braun","year":"2008","journal-title":"Cancer Res"},{"key":"ref56","article-title":"Inverse Association between miR-194 Expression and Tumor Invasion in Gastric Cancer.","author":"Y Song","year":"2011"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"10105","DOI":"10.1158\/0008-5472.CAN-08-1846","article-title":"Coordinated regulation of cell cycle transcripts by p53-Inducible microRNAs, miR-192 and miR-215.","volume":"68","author":"SA Georges","year":"2008","journal-title":"Cancer Res"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/1476-4598-10-99","article-title":"MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1.","volume":"10","author":"P Dong","year":"2011","journal-title":"Mol Cancer"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ydbio.2010.06.027","article-title":"Distinct developmental roles for direct and indirect talin-mediated linkage to actin.","volume":"345","author":"A Franco-Cea","year":"2010","journal-title":"Dev Biol"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1126\/science.1163865","article-title":"The tail of integrins, talin, and kindlins.","volume":"324","author":"M Moser","year":"2009","journal-title":"Science"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1006\/bbrc.2001.5497","article-title":"Analysis of the mammalian talin2 gene TLN2.","volume":"286","author":"SJ Monkley","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nature01147","article-title":"Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin.","volume":"420","author":"G Di Paolo","year":"2002","journal-title":"Nature"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1083\/jcb.142.4.1121","article-title":"Disruption of the talin gene compromises focal adhesion assembly in undifferentiated but not differentiated embryonic stem cells.","volume":"142","author":"H Priddle","year":"1998","journal-title":"J Cell Biol"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1038\/ncb1765","article-title":"Talin depletion reveals independence of initial cell spreading from integrin activation and traction.","volume":"10","author":"X Zhang","year":"2008","journal-title":"Nat Cell Biol"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.ydbio.2010.11.010","article-title":"Endothelial cell talin1 is essential for embryonic angiogenesis.","volume":"349","author":"SJ Monkley","year":"2010","journal-title":"Dev Biol"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1158\/0008-5472.CAN-09-2833","article-title":"Talin1 promotes tumor invasion and metastasis via focal adhesion signaling and anoikis resistance.","volume":"70","author":"S Sakamoto","year":"2010","journal-title":"Cancer Res"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1159\/000330734","article-title":"Identification by differential tissue proteome analysis of talin-1 as a novel molecular marker of progression of hepatocellular carcinoma.","volume":"80","author":"H Kanamori","year":"2011","journal-title":"Oncology"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.bbrc.2011.01.109","article-title":"Integrin alphabeta1, alphavbeta, alpha6beta effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance.","volume":"406","author":"HA Sansing","year":"2011","journal-title":"Biochem Biophys Res Commun"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"e31422","DOI":"10.1371\/journal.pone.0031422","article-title":"Trastuzumab Produces Therapeutic Actions by Upregulating miR-26a and miR-30b in Breast Cancer Cells.","volume":"7","author":"T Ichikawa","year":"2012","journal-title":"PLoS One"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0041170","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T05:26:49Z","timestamp":1561958809000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0041170"}},"subtitle":[],"editor":[{"given":"Ming","family":"Tan","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2012,7,19]]},"references-count":69,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2012,7,19]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0041170","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,7,19]]}}}